vidutolimod (CMP-001) / Kuros, Xoma, Regeneron - LARVOL DELTA

Pre-ispy trial: a phase i/ib oncology platform program (pre-i-spy-p1) nct05868226 (SABCS 2025) - P1 | "The current arms under study are PRE1 ALX-148/T-DXd; PRE2 tucatinib/zanidatamab; and PRE3 vidutolimod/cemiplimab. Conclusion The PRE-ISPY phase I/Ib trial has been successfully implemented nationally as part of the Consortium of I-SPY trials. Once safety is established, promising regimens can be rapidly transitioned to I-SPY2.2, K-SPY or other phase II/III trials."

P1 data • Breast Cancer

In vitro characterization of cellular responses elicited by endosomal TLR agonists encapsulated in Qβ virus-like particles. (PubMed, BMC Immunol) - "In summary, endosomal TLRa VLPs all have the ability to activate pDCs, however, combined TLR7/8 activation using TLR7/8a VLPs was significantly more effective than the other VLPs at activating T cells and was dependent on direct contact with pDCs. Therefore, TLR7/8a VLPs may potentially induce a robust anti-tumor immune response and warrant further investigation for cancer therapy."

Journal • Preclinical • Oncology • CD4 • CD8 • IFNA1 • IFNG • TLR8 • TNFA

Treatment with Virus-like particles containing a TLR9-agonist enhances and extends the activation of tumor-specific CD8+ T cells (SITC 2025) - "Vidutolimod also increased the frequency of circulating PD-1+ OT-1 T cells, supporting further evaluation of anti-PD-1 therapy in combination with Vidutolimod. Taken together, our findings highlight the immunostimulatory effects of Vidutolimod on tumor-specific CD8+ T cells and provides insight into prior studies that demonstrated an enhanced anti-tumor response with Vidutolimod treatment, especially in combination with anti-PD-1 therapy.Ethics Approval Mouse studies were approved by and performed according to guidelines established by the University of Iowa Institutional Animal Care and Use Committee under an approved IACUC Protocol #3011236."

IO biomarker • Oncology • CD8 • GZMB • IFNG • IL2RA

Preclinical characterization of a first-in-class RNA/DNA hybrid TLR7/8/9 agonist, Z-007, ex vivo in human tumor-associated cells, in vivo in mice and primates, and tumor regression in mice. (SITC 2025) - "Recently, vidutolimod, the first CpG-A TLR9 agonist, showed systemic monotherapy activity (9/40 responses) in PD-1 blockade-resistant melanoma.1 In the randomized ECOG-ACRIN EA6194 trial in neoadjuvant melanoma, the addition of vidutolimod induced a 20% increase in pathologic complete response compared to pembrolizumab alone, supporting earlier data in a non-randomized trial.2 3 Vidutolimod is delivered in a viral-like particle that induces neutralizing antibodies,4 5 and vidutolimod resistance in advanced melanoma is associated with TLR7/8+, TLR9- immune suppressive tumor-associated myeloid cells (TAM).6 We hypothesized that co-stimulating TLR7/8/9 with an RNA/DNA mimic of viral replicative complexes in a non-immunogenic LNP may activate TAM and overcome vidutolimod resistance, inducing more effective anti-tumor responses.Methods We designed and synthesized novel native backbone RNA/DNA hybrids to co-stimulate TLR7/8/9. For pharmacodynamics comparison, the corresponding..."

Preclinical • Melanoma • Oncology • Peritoneal Cancer • Solid Tumor • CD8 • CXCL10 • IFNA1

Intratumoural CMP-001 in association with nivolumab in patients with high-risk resectable melanoma (EADV 2025) - No abstract available

Clinical • Melanoma • Oncology • Solid Tumor

Vidutolimod (CMP-001) in Combination With Nivolumab for the Treatment of Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=10 | Suspended | Sponsor: Emory University | Trial completion date: Jun 2027 ➔ Jun 2028

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Intratumoral vidutolimod as monotherapy or in combination with pembrolizumab in patients with programmed cell death 1 blockade-resistant melanoma: Final analysis from a phase 1b study. (PubMed, Cancer) - "Vidutolimod PS20-A alone or in combination with pembrolizumab had an acceptable safety profile and promising clinical activity in patients with PD-1 blockade-resistant melanoma."

Journal • Monotherapy • P1 data • Melanoma • Oncology • Solid Tumor • PD-1

Vidutolimod Combo Therapy Shows Promise in Treating Advanced Melanoma (DermatologyTimes) - P1b | N=199 | NCT02680184 | Sponsor: Regeneron Pharmaceuticals | "This open-label, multicenter phase 1b trial (NCT02680184) consisted of two parts. Part 1 tested vidutolimod with pembrolizumab in 159 patients, and part 2 tested vidutolimod monotherapy in 40 patients....The most clinically meaningful responses were observed with the PS20-A formulation. Over 7.1% of patients had a complete response with the best objective response rate of 23.5%. The median duration of response was 25.2 months with median overall survival of 16.3 months. Responses were seen in both injected and noninjected lesions, including in visceral metastases, suggesting systemic immune activation. Notably, 12 patients treated with PS20-A plus pembrolizumab had responses lasting over a year, with two maintaining responses beyond 36 months. In contrast, the PS20-B formulation had a lower efficacy of 11.5%. The median duration of response was 11.4 months."

P1 data • Melanoma

Clinical Study of CMP-001 in Combination With Pembrolizumab or as a Monotherapy (clinicaltrials.gov) - P1 | N=199 | Completed | Sponsor: Regeneron Pharmaceuticals | Phase classification: P1b ➔ P1

Monotherapy • Phase classification • Melanoma • Oncology • Solid Tumor

A phase II randomized study of neoadjuvant pembrolizumab (P) alone or in combination with vidutolimod (V) in high-risk resectable melanoma: ECOG-ACRIN EA6194. (ASCO 2025) - P2 | "Neoadjuvant P + V demonstrated acceptable safety and encouraging clinical activity in pts with resectable clinical stages IIIB/IIIC/IIID melanoma when considering Arm A and historical controls, warranting further investigation. *4 on Arm A and 1 on Arm B did not have surgery due to PD."

Clinical • Combination therapy • Late-breaking abstract • P2 data • Cardiovascular • Diabetes • Hematological Disorders • Hypertension • Hypotension • Melanoma • Oncology • Pain • Solid Tumor

Regeneron to Highlight Advances at ASCO with Phase 3 Adjuvant Libtayo (cemiplimab) CSCC Updates and Promising Early Blood Cancer Data with Linvoseltamab Combination (GlobeNewswire) - "Eighteen presentations will share the latest insights from ongoing research of approved and investigational treatment regimens across a range of difficult-to-treat cancers including non-melanoma and melanoma skin cancer, lung cancer, lymphoma and multiple myeloma...Notable presentations at ASCO on Regeneron’s oncology pipeline include detailed efficacy and safety findings from the Phase 3 C-POST trial evaluating the adjuvant use of the PD-1 inhibitor Libtayo in post-surgical high-risk cutaneous squamous cell carcinoma (CSCC). The results will be presented in an oral session on Saturday, May 31...Regeneron will debut results from two cohorts of the LINKER-MM2 trial...which will be featured in two rapid oral presentations on Monday, June 2...In addition, the results of a cooperative group study reporting on the primary analysis of a randomized Phase 2 trial of vidutolimod..."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy of Treatment in Patients With Operable Melanoma (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Biomarker • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

In situ treatment with a TLR9 agonist virus-like particle to promote immune responses against oral epithelial dysplasia progression. (PubMed, Cancer Immunol Immunother) - "ELISA revealed significantly elevated levels of IFN-γ, IL-12, and TNF-α in the sera of mice after 24 h of one treatment with vidutolimod + ICB as well as increased levels of proliferating T cells and pDCs in draining lymph nodes 72 h after the third and final treatment, thus indicating the immune-boosting effect of this therapy. Vidutolimod + ICB caused a significant decrease in Ki-67 expression by epithelial cells in the lesion area compared to untreated mice, implicating that this treatment regime may prevent lesion progression."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • IFNG • IL12A • TLR9 • TNFA

A Phase 2, Open-Label Study of Intratumoral Vidutolimod in Combination With Intravenous Pembrolizumab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (COSM 2025) - P2 | "Vidutolimod plus pembrolizumab had a generally manageable safety profile and demonstrated durable disease control among responders in PD-1 inhibitor-naive patients with R/M HNSCC."

Clinical • Combination therapy • Metastases • P2 data • Constipation • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Head and Neck Cancer • Hypotension • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov) - P1/2 | N=14 | Completed | Sponsor: Umar Farooq | Active, not recruiting ➔ Completed | N=39 ➔ 14 | Trial completion date: Apr 2026 ➔ Apr 2025

Enrollment change • Trial completion • Trial completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

A Multicentre, Open-Label, Phase 2 Study of Intratumoural Vidutolimod in Combination with Intravenous Nivolumab in Patients with Refractory, Unresectable or Metastatic Melanoma: Clinical and Correlative Results (EADO-WCM 2025) - P2 | "Conclusions Vidu IT + anti–PD-1 therapy had modest antitumour activity in PD-1 blockade−resistant melanoma pts in this study, suggesting a need for predictive biomarkers in future studies. Treatment led to a notable transient increase in IFN⍺ levels and induced type I/II interferon signalling, consistent with vidu's proposed mechanism of action."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • CXCL10 • IFNG • IL10 • IL6

A Phase 2, Open-Label Study of Intratumoral Vidutolimod in Combination With Intravenous Pembrolizumab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (AHNS-COSM 2025) - P2 | "Vidutolimod plus pembrolizumab had a generally manageable safety profile and demonstrated durable disease control among responders in PD-1 inhibitor-naive patients with R/M HNSCC."

Clinical • Combination therapy • Metastases • P2 data • Constipation • Endocrine Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Head and Neck Cancer • Hypotension • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CMP-001 and Pre-operative Stereotactic Body Radiation Therapy (SBRT) in Early Stage Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: Centre Hospitalier Universitaire Vaudois | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Sep 2023 ➔ Dec 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy of Treatment in Patients With Operable Melanoma (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Biomarker • Enrollment closed • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov) - P1/2 | N=39 | Active, not recruiting | Sponsor: Umar Farooq | Suspended ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy in Patients With Operable Melanoma (clinicaltrials.gov) - P2 | N=60 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Biomarker • Combination therapy • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

CMP-001 for Relapsed and Refractory Lymphoma (clinicaltrials.gov) - P1/2 | N=39 | Active, not recruiting | Sponsor: Umar Farooq | Trial primary completion date: Apr 2025 ➔ Aug 2024

Trial primary completion date • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial. (PubMed, Cancer Cell) - P2 | "Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641."

IO biomarker • Journal • P2 data • Infectious Disease • Melanoma • Oncology • Solid Tumor • CD8

Intratumoral vidutolimod in combination with PD-1 blockade in locoregionally advanced melanoma. (PubMed, Cancer Cell) - "In this issue of Cancer Cell, Davar and colleagues report a promising phase 2 neoadjuvant trial of the TLR9 agonist vidutolimod in combination with nivolumab. Analyses suggest a unique myeloid expression signature is associated with response."

Combination therapy • IO biomarker • Journal • Metastases • Melanoma • Oncology • Solid Tumor

Intratumoral injection of vidutolimod, an immunostimulatory virus-like particle, enhances the number of intratumoral and circulating tumor-specific CD8 T cells (SITC 2024) - "Conclusions Vidutolimod induced a greater influx of OT-1 T cells into the primary tumor and in circulation which supports previous studies that saw an abscopal effect of non-treated tumors. Vidutolimod also increased the number of circulation PD-1+ OT-1 T cells which supports clinical research of anti-PD-1 therapy in combination with vidutolimod Ethics Approval Mouse studies were approved by and performed according to guidelines established by the University of Iowa Institutional Animal Care and Use Committee under an approved IACUC Protocol #3011236."

IO biomarker • Oncology • CD4 • CD8